Gut microbiome modified by bariatric surgery improves insulin sensitivity and correlates with increased brown fat activity and energy expenditure

Jitender Yadav, Tao Liang, Tairan Qin, Nayanan Nathan, Katherine J.P. Schwenger, Lauren Pickel, Li Xie, Helena Lei, Daniel A. Winer, Heather Maughan, Susan J. Robertson, Minna Woo, Wendy Lou, Kate Banks, Timothy Jackson, Allan Okrainec, Susy S. Hota, Susan M. Poutanen, Hoon-Ki Sung, Johane P. Allard, Dana J. Philpott, and Herbert Y. Gaisano

Cell Rep Med 2023 May 16;4(5):101051. doi: 10.1016/j.xcrm.2023.101051

Pubmed: 37196633


Alterations in the microbiome correlate with improved metabolism in patients following bariatric surgery. While fecal microbiota transplantation (FMT) from obese patients into germ-free (GF) mice has suggested a significant role of the gut microbiome in metabolic improvements following bariatric surgery, causality remains to be confirmed. Here, we perform paired FMT from the same obese patients (BMI > 40; four patients), pre- and 1 or 6 months post-Roux-en-Y gastric bypass (RYGB) surgery, into Western diet-fed GF mice. Mice colonized by FMT from patients’ post-surgery stool exhibit significant changes in microbiota composition and metabolomic profiles and, most importantly, improved insulin sensitivity compared with pre-RYGB FMT mice. Mechanistically, mice harboring the post-RYGB microbiome show increased brown fat mass and activity and exhibit increased energy expenditure. Moreover, improvements in immune homeostasis within the white adipose tissue are also observed. Altogether, these findings point to a direct role for the gut microbiome in mediating improved metabolic health post-RYGB surgery.